The single greatest risk factor for cancer is aging. While aging and cancer involve common pathways, the intersection of these biologic processes is not well understood. A greater understanding of the relationship between aging and cancer is of paramount importance given the advancing age of the U.S. population. Currently 35 million Americans are over the age of 65, and this number is expected to double by 2030. The use of high throughput proteomic tools have the potential to advance our understanding of aging and cancer, as they have recently been shown to have the potential for providing highly accurate approaches for the early detection of prostate, ovarian, lung, and head/neck cancers. These studies have garnered considerable interest and enthusiasm given the potential impact early detection of different cancers, through the use of multiple new protein biomarkers, can have on reducing their mortalities and human and economic costs. However, the promise of proteomics can only be realized if these differences are also found in a prospective setting, where samples are obtained prior to the diagnosis of cancer. Existing cohort studies provide an ideal setting for evaluating whether or not current proteomic tools can be used to distinguish between those who will and will not develop cancer. Herein we propose a case-cohort study using a subset of subjects over 65 years of age who have participated in the Cardiovascular Health Study cohort since 1989. Using matrix-assisted laser desoprtion and ionization (MALDI) we will evaluate the proteome of plasma samples that were collected on these subjects at multiple time points. The hypotheses to be tested are: 1) Baseline plasma proteomic patterns can be used to distinguish between subjects who will and will not develop breast, colorectal, lung, and prostate cancers; 2) Addition of known risk factors for different cancers to our proteomic algorithms will enhance their predictive power; 3) Identification of changes in proteomic patterns over time will enhance our understanding of aging and cancer, and improve the predictive power of this approach as a screening test for cancer; 4) Identification of the proteins that distinguish between subjects who did and did not develop these cancers will advance our understanding of their etiologies and possibly aid in their early detection. [unreadable] [unreadable]